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在肝硬化大鼠模型中使用磁共振成像(MRI)追踪氧化铁标记的间充质干细胞(MSCs)。

Tracking iron oxide labelled mesenchymal stem cells(MSCs) using magnetic resonance imaging (MRI) in a rat model of hepatic cirrhosis.

作者信息

Noorwali Abdulwahab, Faidah Mamdooh, Ahmed Naushad, Bima Abdulhadi

机构信息

Stem Cell Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Department of Medical Laboratory,College of Health Sciences,King Abdulaziz University,Jeddah 21589 Saudi Arabia.

出版信息

Bioinformation. 2019 Jan 31;15(1):1-10. doi: 10.6026/97320630015001. eCollection 2019.

Abstract

Homing and tumor attenuation potential of BM-MSCs labelled with superparamagnetic iron-oxide nanoparticles (SPIONs) in a rat model of hepatic cirrhosis was evaluated. Rat BM-MSCs were derived, characterized and labelled with SPIONs (200 nm; 25 mg Fe/ml). Hepatic cirrhosis was induced in Wistar rats (n=30; 10/group) with carbon tetrachloride (CCl4; 0.3 mL/kg body weight) injected twice a week for 12 weeks. Group-I was administered vehicle (castor-oil) alone; Group-II received two doses of unlabelled BM-MSCs (3x106 cells) and Group-III received two doses of SPIONs labelled BM-MSCs (3x106 cells) via tail vein injection (0.5 ml) at weekly intervals. All animals were sacrificed after two weeks for histological, radiological and biochemical analysis. Derived BM-MSCs demonstrated MSCs related CD markers. Histology confirmed induction of hepatic cirrhosis with CCL4. Levels of alanine-aminotransferase, aspartate-aminotransferase,alkaline-phosphatase and gamma glutamyl-transferase returned to normal levels following treatment with BM-MSCs. Uptake and homing of SPIONs labelled BM-MSCs, and reduction in the size of cirrhotic nodules were confirmed using transmission electron microscopy and magnetic resonance imaging respectively. BM-MSCs reduced the pathological effects of CCL4 induced hepatic cirrhosis and labelling BMMSCs with SPIONs were non-toxic and enabled efficient tracking using non-invasive methods.

摘要

评估了超顺磁性氧化铁纳米颗粒(SPIONs)标记的骨髓间充质干细胞(BM-MSCs)在肝硬化大鼠模型中的归巢和肿瘤衰减潜力。从大鼠中分离出BM-MSCs,进行表征并用SPIONs(200nm;25mg Fe/ml)标记。用四氯化碳(CCl4;0.3mL/kg体重)诱导Wistar大鼠(n = 30;每组10只)肝硬化,每周注射两次,共12周。第一组仅给予赋形剂(蓖麻油);第二组接受两剂未标记的BM-MSCs(3×106个细胞),第三组通过尾静脉注射(0.5ml)每周间隔接受两剂SPIONs标记的BM-MSCs(3×106个细胞)。两周后处死所有动物进行组织学、放射学和生化分析。分离出的BM-MSCs显示出与MSCs相关的CD标志物。组织学证实CCl4诱导了肝硬化。用BM-MSCs治疗后,丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶和γ-谷氨酰转移酶水平恢复到正常水平。分别使用透射电子显微镜和磁共振成像证实了SPIONs标记的BM-MSCs的摄取和归巢,以及肝硬化结节大小的减小。BM-MSCs减轻了CCl4诱导的肝硬化的病理影响,用SPIONs标记BM-MSCs无毒,并能够使用非侵入性方法进行有效追踪。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e01/6651036/527acaf00b98/97320630015001F1.jpg

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